CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1601125
This article is part of the Research TopicBrain Metastasis and Systemic Target Therapy: Implications for NeurosurgeonsView all articles
A Stage IV Lung Squamous Cell Cancer Patient with Brain Metastases, High PD-L1 & TMB, Achieves pCR and Long-Term Survival after Immune-Chemotherapy and Radical Surgery: A Case Report and literature review
Provisionally accepted
Xiangyu Xu
Zheng Ma*- Chongqing General Hospital, Chongqing, China
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Brain metastases occur in 40% of advanced NSCLC patients, with poorer prognosis in squamous subtypes. Immune checkpoint inhibitors (ICIs) combined with chemotherapy have revolutionized treatment, yet data on the systematic treatment of stage IV squamous non-small cell lung cancer with surgery remain limited. A 59-year-old male smoker presented with stage cT4N2M1b IVA squamous NSCLC and a solitary brain metastasis. Next-generation sequencing revealed programmed cell death ligand 1 (PD-L1) high expression (TPS=75%) and TMB-High (28.49 Mut/Mb) without driver mutations. After pembrolizumab plus platinum-based chemotherapy induced conversion therapy for 3 cycles, the brain lesion achieved pathological complete response (pCR) following resection, while the primary lung tumor showed major pathological response (MPR) post-surgery. Postoperative adjuvant chemoimmunotherapy and 2-year pembrolizumab maintenance were administered. Serial circulating tumor DNA (ctDNA) monitoring remained negative, with no recurrence observed over 50 months. This is the first reported case of long-term survival (PFS >50 months) in a PD-L1-high/TMB-High squamous NSCLC patient with brain metastasis treated with immunotherapy-based multimodal therapy.Our findings suggest that biomarker-guided strategies integrating systemic therapy, surgery, and MRD monitoring may enable curative potential in select advanced NSCLC patients. Further studies are warranted to validate this "sandwich" approach (drug-surgery-drug) and optimize treatment duration.
Keywords: Non-small cell lung cancer (NSCLC), brain metastasis, Programmed cell death ligand 1, Tumor mutational burden (TMB), pathological complete response (PCR), circulating tumor DNA (ctDNA)
Received: 27 Mar 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Xu and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zheng Ma, Chongqing General Hospital, Chongqing, China
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